Background

Insulinoma-associated protein 1 (INSM1), a transcriptional regulator with a zinc-finger DNA-binding domain, has been validated as a cytoplasmic marker for neuroendocrine differentiation of tumor cells. Next to its abundant expression in the fetal pancreas, it is expressed in brain tumors, pheochromocytomas, medullary thyroid carcinomas, insulinomas and pituitary and small-cell lung carcinomas. INSM1 is not expressed in normal adult tissues and/or most non-neuroendocrine tumors. It regulates various downstream signaling pathways, including the Sonic Hedgehog, PI3K/AKT, MEK/ERK1/2, ADK, p53, Wnt, histone acetylation, LSD1, cyclin D1, Ascl1 and N-Myc pathways. Although INSM1 appears to be a subtle and specific biomarker for neuroendocrine tumors, its role in tumor development has remained unclear.

Conclusions

Here, we highlight INSMI expression, as well as its diagnostic significance and use as a therapeutic target in various neuroendocrine tumors. Targeting signaling pathways or gene expression alterations associated with INSM1 expression may be instrumental for the design of novel therapeutic strategies for neuroendocrine tumors.

中文翻译：

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胰岛素瘤相关蛋白1（INSM1）：神经内分泌肿瘤的潜在生物标志物和治疗靶标。

背景

胰岛素瘤相关蛋白1（INSM1），具有锌指DNA结合结构域的转录调节子，已被证实是肿瘤细胞神经内分泌分化的细胞质标记。除了在胎儿胰腺中大量表达外，它还可以在脑肿瘤，嗜铬细胞瘤，甲状腺髓样癌，胰岛素瘤以及垂体和小细胞肺癌中表达。在正常的成人组织和/或大多数非神经内分泌肿瘤中不表达INSM1。它调节各种下游信号传导途径，包括Sonic Hedgehog，PI3K / AKT，MEK / ERK1 / 2，ADK，p53，Wnt，组蛋白乙酰化，LSD1，cyclin D1，Ascl1和N-Myc途径。尽管INSM1似乎是神经内分泌肿瘤的微妙和特异性的生物标志物，但其在肿瘤发展中的作用仍不清楚。

结论

在这里，我们重点介绍INSMI表达及其诊断意义，并将其用作各种神经内分泌肿瘤的治疗靶标。与INSM1表达相关的靶向信号通路或基因表达改变可能有助于设计神经内分泌肿瘤的新型治疗策略。